Biomedical subjects

Jonas Persson

Publications and source records attributed to Jonas Persson.

13 recordsLinked to original sources

PubMed2007

Cognitive fatigue of executive processes: interaction between interference resolution tasks.

A resource depletion framework motivated a novel strategy for investigating whether the central executive is unitary or separable into relatively independent subprocesses. The idea that tasks with overlapping neural representations may involve similar executive components was also critical to our approach. Of particular interest were tasks requiring resolution of interference among competing representations. Within a single experimental session intensive training reduced the ability to resolve interference on a transfer task if the training task placed high demands on interference resolution. Negative transfer was absent when interference resolution was minimally required by the task, or when the training and transfer tasks did not rely on overlapping neural representations. These results suggest a nonunitary central executive composed of separable subcomponents, at least one of which mediates interference resolution. Our results are consistent with an executive control process specialized for the selection of task-relevant representations from competitors. The results also agree with the view that higher cognitive processes are resource limited and can be temporarily depleted.

Adolescent↗

PubMed2006

Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon4 carriers.

Apolipoprotein E-epsilon4 is the main known genetic risk factor for Alzheimer's disease. Functional abnormalities in the parietal cortex have been reported for Alzheimer's disease patients and also for those at risk. Hence, a critical question is whether measurements of parietal cortex integrity may predict negative outcome among at-risk persons. We studied nondemented apolipoprotein E-epsilon4 carriers and found a significant relationship between parietal blood-oxygen-level-dependent functional magnetic resonance imaging response during a word categorization task and subsequent episodic memory performance. Thus, the results show that parietal cortex alterations predict memory decline in nondemented apolipoprotein E-epsilon4 carriers, and hence likely progression to Alzheimer's disease.

Aged↗

PubMed2006

Antigens for the selection of pan-variable number of tandem repeats motif-specific human antibodies against Mucin-1.

Epitopes found on Mucin-1 are differentially expressed on tumour versus normal tissue. Such epitopes have also been shown to have a potential in immunotherapy and tumour detection. The major epitope explored in this context is located within the variable number of tandem repeats. It has however recently been demonstrated that this epitope exists in several sequence variants. The standard sequence is highly antigenic while the most common sequence variant is much less so. We have now explored routes employing defined synthetic antigens to ensure the development of human recombinant antibody specificities targeting both sequence variants of this epitope. These antibodies may serve as a platform for the development of human antibodies for efficient targeting of Mucin-1 in human disease.

Antibodies, Monoclonal↗

PubMed2006

Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers.

The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

Aged↗

PubMed2006

Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory.

Apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE epsilon4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition-memory performance between AD-symptom-free carriers (N=30) and non-carriers (N=30) of the APOE epsilon4 (age range: 49-79 years). We observed reduced right hippocampal volume in APOE epsilon4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE epsilon4 carriers made significantly more false alarms in the recognition-memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

Age Factors↗

PubMed2006

Altered brain activity in healthy seniors: what does it mean?

Age-related performance decreases are frequently observed on various memory tasks. Recent brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggest a link between altered patterns of brain activity in older adults and memory performance. Convergent neuroimaging evidence shows that older adults have decreased activity in multiple regions important for memory tasks. Such relative under-activation in older adults is likely related to age-related reductions in cognitive performance. Age-comparative neuroimaging studies have also provided convincing support for regional over-activation by older adults. Such findings indicate that the older brain can re-organize to better cope with cognitive and other challenges. Although over-activation may play a compensatory role when cognitive decline is limited, under-activation seems to be the typical pattern when cognitive impairment is in a more progressed state. This pattern of age-related changes suggests that compensation through over-activation is restricted to the early stages of cognitive impairment in aging.

Aged↗

PubMed2005

Structure-function correlates of cognitive decline in aging.

To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

Adaptation, Physiological↗

PubMed2005

Subtle sequence differences in a tumour-associated peptide epitope translate into major changes in antigenicity.

Antigenicity, the ability to bind to members of repertoire of diverse immune receptors, is a concept that is poorly characterised with respect to its defining parameters. To learn more about its makeup, we have investigated the ability of two peptides with highly related sequences, derived from the tumour-associated antigen mucin-1, to recruit in vitro members from a large naïve repertoire of synthetic human antibody fragments. One of the peptides represents the epitope that is immunodominant in mice. We now demonstrate that the other peptide, which differs from the first only by a very conservative aspartate-threonine to glutamate-serine change, is much less antigenic than the first peptide. This is so despite the fact that there is no observable difference in the tendency of the two peptides to adopt a structure in solution. Furthermore, the peptides differ in their immunodominant parts and the less antigenic peptide selects for antibody fragments targeting residues outside of the epitope considered to be immunodominant in mice. We conclude that subtle sequence changes greatly, affect antigenicity and immunodominance of epitopes in this important tumour-associated antigen.

Amino Acid Sequence↗

PubMed2004

Selection requirements during verb generation: differential recruitment in older and younger adults.

Age-related differences in cognitive performance are well documented. These differences are most pronounced during tasks with high demands on cognitive control, and it has been proposed that selective alteration of prefrontal activity is associated with cognitive changes in old age. Here, differences in the neural systems underlying selection requirements for older and younger adults were investigated using functional magnetic resonance imaging (fMRI). A verb generation task was used, and selection requirements were varied with regard to whether each noun could be associated with either few (scissors-cut) or many (ball-bounce, kick, throw...) competing alternatives. The two age groups showed statistically equivalent behavioral performance across the task conditions but marked differences in activation. Across both age groups, high selection demands activated several regions including bilateral frontal, left anterior frontal, left inferior temporal regions, and the dorsal anterior cingulate cortex (ACC). Between-group comparisons using region-of-interest analyses revealed less activation for senior adults in left inferior frontal gyrus (IFG), left inferior temporal gyrus, and the anterior cingulate and higher activation in right inferior frontal gyrus compared to young adults. These findings indicate age-related changes in multiple regions contributing to aspects of selection requirements during verb generation.

Adolescent↗

PubMed2003

The memory-enhancing effects of Ginseng and Ginkgo biloba in healthy volunteers.

RATIONALE: The use of herbal remedies, such as Ginkgo biloba and Ginseng, for improving cognitive performance has become increasingly popular during recent years. Several previous studies have indicated that administration of Ginkgo biloba and Ginseng may improve aspects of learning and memory in healthy volunteers. These results, however, are generally not supported by well-controlled clinical studies. Also, positive results have often been reported from studies investigating effects related to short-term, chronic administration of the extract. Nonetheless, both Ginkgo biloba and Ginseng are marketed as having the capacity to enhance cognitive functions, such as memory and learning, in the long term. OBJECTIVE: This study aimed at investigating whether the use of Ginkgo biloba and Ginseng for a long period of time has positive effects on performance on learning and memory. METHODS: Community-dwelling volunteers ( n=3500) from The Betula prospective cohort study: memory, health, and aging were included in the study. RESULTS: It was found that the use of neither Ginkgo biloba ( n=40) nor Ginseng ( n=86) was associated with enhanced memory performance in any of the eight memory tests examined, relative to control groups either using or not using nutritional supplements. CONCLUSIONS: These findings indicate that use of Ginkgo biloba or Ginseng does not provide any quantifiable beneficial effects on memory performance in the long-term in healthy adult volunteers.

Adult↗

PubMed2003

Common prefrontal activations during working memory, episodic memory, and semantic memory.

Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribution of the PFC regions and the architecture of memory.

Adult↗

PubMed2002

Decreased activity in inferotemporal cortex during explicit memory: dissociating priming, novelty detection, and recognition.

Studies of non-human primates have shown that activity in inferotemporal (IT) brain regions decrease over repeated stimulus exposure, a phenomenon known as repetition suppression. In the present study, repetition suppression was examined during recognition of personally experienced events (explicit memory). Brain activity was measured while subjects encoded and subsequently recognized scenic pictures. First, two recognition conditions were compared; one that mainly included familiar pictures and one that mainly included novel pictures. Responses derived from this contrast may reflect recognition memory, perceptual priming, or novelty detection. To test specifically for responses associated with recognition memory, subjects encoded a new set of pictures followed by two recognition tests. All test pictures had been presented during the course of the experiment, and the subjects identified pictures that appeared in the second encoding list. Since all pictures were familiar, repetition suppression was specifically associated with recognition memory. In the first contrast, relative change in brain activity was observed in inferotemporal, extra-striate, and hippocampal regions during recognition of familiar versus novel pictures. In the second contrast, decreased activity in IT cortex was found. The location of this region overlapped with that for the region identified in the first contrast, and a conjunction analysis showed that reduced activity in left IT cortex was common to both contrasts. These results suggest that repetition suppression in IT cortex reflects recognition memory, and that such a response is not a simple function of stimulus repetition but can be modulated by top-down processing.

Adult↗

PubMed2002

Individual differences in memory enhancement by encoding enactment: relationships to adult age and biological factors.

Numerous studies have demonstrated an age-related decline in episodic memory performance. However, both younger and older adults benefit from various kinds of encoding support, suggesting that memory functioning remains plastic in older age. The present review is concerned with encoding support in the form of enactment. Memory for simple commands is substantially higher if the commands are enacted during encoding than only read/heard. Such memory enhancement has been demonstrated for many age groups and patient groups, suggesting that it is a general effect. Analysis of the results from 1000 participants ranging in age between 35 and 80 years revealed that about 5% of the participants had low memory performance after enacted encoding and showed no enactment effect. The majority of these were older. Comparisons of participants that did or did not show an enactment effect for a select set of biological and neuropsychological factors provided tentative evidence that a failure to benefit from encoding enactment reflects a dysfunctional motor system. This is in agreement with findings from recent functional neuroimaging studies that associate the enactment effect with motor areas in the brain. Variation in the ability to benefit from encoding enactment is discussed in relation to an age-related decline in dopamine function.

Aging↗